DNA Methyltransferase 3A Is Involved in the Sustained Effects of Chronic Stress on Synaptic Functions and Behaviors.

Autor:	Wei J; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA., Cheng J; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA., Waddell NJ; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA., Wang ZJ; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA., Pang X; Department of Statistics, Florida State University, Tallahassee, FL 32306, USA., Cao Q; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA., Liu A; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA., Chitaman JM; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA., Abreu K; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA., Jasrotia RS; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA., Duffney LJ; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA., Zhang J; Department of Statistics, Florida State University, Tallahassee, FL 32306, USA., Dietz DM; Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, NY 14203, USA., Feng J; Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, USA., Yan Z; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14203, USA.
Jazyk:	angličtina
Zdroj:	Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2021 Mar 05; Vol. 31 (4), pp. 1998-2012.
DOI:	10.1093/cercor/bhaa337
Abstrakt:	Emerging evidence suggests that epigenetic mechanisms regulate aberrant gene transcription in stress-associated mental disorders. However, it remains to be elucidated about the role of DNA methylation and its catalyzing enzymes, DNA methyltransferases (DNMTs), in this process. Here, we found that male rats exposed to chronic (2-week) unpredictable stress exhibited a substantial reduction of Dnmt3a after stress cessation in the prefrontal cortex (PFC), a key target region of stress. Treatment of unstressed control rats with DNMT inhibitors recapitulated the effect of chronic unpredictable stress on decreased AMPAR expression and function in PFC. In contrast, overexpression of Dnmt3a in PFC of stressed animals prevented the loss of glutamatergic responses. Moreover, the stress-induced behavioral abnormalities, including the impaired recognition memory, heightened aggression, and hyperlocomotion, were partially attenuated by Dnmt3a expression in PFC of stressed animals. Finally, we found that there were genome-wide DNA methylation changes and transcriptome alterations in PFC of stressed rats, both of which were enriched at several neural pathways, including glutamatergic synapse and microtubule-associated protein kinase signaling. These results have therefore recognized the potential role of DNA epigenetic modification in stress-induced disturbance of synaptic functions and cognitive and emotional processes. (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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